Veterans returning home from recent engagements in Iraq and Afghanistan represent a vulnerable population at disproportionate risk of prescription opioid (PO) misuse and overdose. As current research is demonstrating, these risks are potentially even higher for women, minority, homeless, and otherwise socially isolated veterans, as well as those with mental health concerns. Despite these preliminary findings about the clustering of opioid- related risks among particular veteran subpopulations, very little is currenty known about how these risks emerge over time and what conditions and events precipitate them. This project represents one of the first to address the emergence of opioid-related risk behaviors over time and to track the changing dimensions of veterans' reintegration experiences that impact PO and other substance use patterns. Accordingly, this study will track opioid-using veterans' substance use patterns alongside other physiological, psychological, and social dimensions of their lives, ranging from post-traumatic stress disorder (PTSD) symptoms, depression, and pain severity to social relationships and employment status. The study will provide critical insights into the stressors, turning points, and substance use patterns that precede emergence of overdose risk behaviors and the protective factors that keep some opioid-using veterans safe despite their struggles with pain and the psychosocial challenges of reintegration. To do so, it will investigate the following aims: Aim A: Identify key contextual dimensions of opioid-related overdose risk among veterans. Qualitative interviews will be administered to 50 recent veterans who have received prescription opioids for pain and who have experienced at least one non-fatal overdose involving opioids. The data obtained will illuminate the relationships among pain, opioid medications, mental health concerns, life stressors, and overdose risk. These data will inform instrument design and refinement for Aims B and C. Aim B: Identify biological, psychological and social factors related to veterans' transitions into and out of overdose risk over time. The project will survey 250 PO-using recent veterans and follow them for two years, collecting monthly data using interactive voice response (IVR) technology in order to: 1) Develop an Overdose Risk Behavior Scale (ORBS) based on the literature, existing scales for aberrant PO use, known overdose risks, and common risks among veterans (especially as identified in Aim A); and 2) Test hypotheses regarding potential biopsychosocial (BPS) correlates of overdose risk behavior. Aim C: Identify veterans' subjective perceptions of changes in overdose risk over time and how these contribute to the mechanisms underlying changes in opioid use patterns. Ongoing qualitative interviews with an embedded subsample of 32 veterans will provide an important supplement to the findings from Aim B, revealing veterans' subjective perceptions, understandings and misunderstandings that accompany changes in pain, mental health and social support, thus providing a foundation underlying changes in overdose risk.